NPM / ALK, p80, Anaplastic Lymphoma Kinase

The ALK protein is probably a tyrosine kinase receptor for the growth factor pleiotrophin3. The normal ALK protein is 200kD6. The majority of anaplastic large cell lymphomas are associated with the t(2;5)(p23;q35) translocation13, which results in the fusion of the cell cycle regulating nucleolar protein nucleophosmin (NPM) with the anaplastic lymphoma kinase (ALK), producing an 80 kD chimeric protein6, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the ALK protein11. The antibody ALK1 recognises an intracellular domain of the ALK protein14. ALK-1, ALKc and p80 all react with both normal ALK and the NPM-ALK fusion protein. ALK-11 is a rabbit polyclonal anti-human antibody against the ALK protein4.

Immunohistochemical expression

anaplastic large cell lymphoma

180/213, 39/736, 43/6710, 60/10011, 19/2012

Diffuse large B-cell lymphoma with expression of full-length ALK


Diffuse large B-cell lymphoma with expression of full-length Clathrin-ALK fusion product

3/315, 6/616

T-cell lymphoma


B-cell lymphoma

 0/100, 1/1712

Hodgkin's disease

0/80, negative6, 0/6310, 0/612

Lymphomatoid papulosis


Inflammatory myofibroblastic tumour

44/734, 4/108, 31/5517

reactive lymphoid tissue


alveolar rhabdomyosarcoma

14/317, 4/168

embryonal rhabdomyosarcoma


mixed alveolar / embryonal rhabdomyosarcoma


pleomorphic rhabdomyosarcoma


unclassified rhabdomyosarcoma

1/27, 2/158

rhabdomyosarcomatous component of mixed Mullerian tumour






malignant fibrous histiocytoma



Positivity for ALK in Inflammatory myofibroblastic tumour and rhabdomyosarcoma is associated with extra copies of 2p23 and ALK break-apart or ALK/NPM fusion, as demonstrated by FISH8.

Diagnostic utility


1 Delsol G, New antibodies and new applications of old antibodies in the diagnosis of hematolymphoid neoplasms. In Immunohistochemistry Long Course, Nice, October 18-23, 1998.

2 ten Berge, R. L., Snijdewint, F. G., von Mensdorff-Pouilly, S. MUC1 (EMA) is preferentially expressed by ALK positive anaplastic large cell lymphoma, in the normally glycosylated or only partly hypoglycosylated form. J Clin Pathol 2001;54:933-939. FULL TEXT

3 Stoica, G. E., Kuo, A., Aigner, A. Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. J Biol Chem 2001;276:16772-9. FULL TEXT

4 Cook, J. R., Dehner, L. P., Collins, M. H., Ma, Z., Morris, S. W., Coffin, C. M., Hill, D. A. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001;25:1364-1371.

5 Christie Problems in Tumour Patholgy, 7.6.2002.

6 Pulford, K., Lamant, L., Morris, S. W. et al. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood 1997;89:1394-404.

7 Pillay, K., D. Govender, et al. (2002). "ALK protein expression in rhabdomyosarcomas." Histopathology 41(5): 461-7. (Initialy published as Pillay K, Bickhoo A, Govender D, Chetty R. ALK protein expression in rhabdomyosarcomas. Pathological Society July 2002, abstract 171.)

8 Cessna, M. H., H. Zhou, et al. (2002). "Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases." Mod Pathol 15(9): 931-8. (Initially published as Coffin CM et al. Expression of ALK 1 and p80 in inflammatory myofibroblastic tumour and its mimics. A study of 135 cases. Mod Pathol 2001;14:10A.)

9 Cataldo KA, Jalal SM, Law ME, et al. Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue. Am J Surg Pathol 1999; 23:1386-92

10 Nakamura S, Shiota M, Nakagawa A, et al. Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression. Am J Surg Pathol 1997; 21:1420-32

11 Falini B, Bigerna B, Fizzotti M, et al. ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum. Am J Pathol 1998; 153:875-86

12 Hutchison RE, Banki K, Shuster JJ, et al. Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood. Ann Oncol 1997; 8 Suppl 1:37-42

13 Lamant L, Meggetto F, al Saati T, et al. High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining. Blood 1996; 87:284-91

14 Delsol G, Lamant L, Mariame B et al.  A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2;5 translocation.   Blood 1997;89:1483-90. FULL TEXT

15 De Paepe P, Baens M, van Krieken H, et al. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 2003; 102:2638-41 FULL TEXT

16 Gascoyne RD, Lamant L, Martin-Subero JI, et al. ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases. Blood 2003; 102:2568-73 FULL TEXT

17 Coffin CM, Hornick JL,Fletcher CD Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007; 31:509-20


This page last revised 30.4.2007.

©SMUHT/PW Bishop